15-87880105-AT-A

Position:

• chr15-87880105-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001012338.3(NTRK3):​c.2334+164del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 148,670 control chromosomes in the GnomAD database, including 181 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.027 (181 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.640

Genes affected

NTRK3 (HGNC:8033): (neurotrophic receptor tyrosine kinase 3) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-87880105-AT-A is Benign according to our data. Variant chr15-87880105-AT-A is described in ClinVar as [Benign]. Clinvar id is 1236984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.2334+164del		intron_variant		ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.2334+164del		intron_variant		1	NM_001012338.3	ENSP00000485864

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 3950 AN: 148586 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000640

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.00142

Gnomad OTH AF: 0.0198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0266 AC: 3955 AN: 148670 Hom.: 181 Cov.: 32 AF XY: 0.0251 AC XY: 1820 AN XY: 72430

Gnomad4 AFR AF: 0.0887

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000643

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.0196

Alfa AF: 0.000613 Hom.: 0

Bravo AF: 0.0302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5814311; hg19: chr15-88423336;